Abstract
Carbon dioxide (CO2) is a key molecule in many biological processes; however, mechanisms by which organisms sense and respond to high CO2 levels remain largely unknown. Here we report that acute CO2 exposure leads to a rapid cessation in the contraction of the pharynx muscles in Caenorhabditis elegans. To uncover the molecular mechanisms underlying this response, we performed a forward genetic screen and found that hid-1, a key component in neuropeptide signaling, regulates this inhibition in muscle contraction. Surprisingly, we found that this hid-1-mediated pathway is independent of any previously known pathways controlling CO2 avoidance and oxygen sensing. In addition, animals with mutations in unc-31 and egl-21 (neuropeptide secretion and maturation components) show impaired inhibition of muscle contraction following acute exposure to high CO2 levels, in further support of our findings. Interestingly, the observed response in the pharynx muscle requires the BAG neurons, which also mediate CO2 avoidance. This novel hid-1-mediated pathway sheds new light on the physiological effects of high CO2 levels on animals at the organism-wide level.
Highlights
One of the fundamental features shared by most, if not all, living organisms is the ability to maintain levels of carbon dioxide (CO2)
Using Caenorhabditis elegans as a model system, we found that exposure to high CO2 levels leads to a very rapid cessation in the contraction of the pharynx muscles
Further analysis revealed that the pharynx muscle response is controlled by dense core vesicle secretion from the BAG neurons in a hid-1-mediated pathway
Summary
One of the fundamental features shared by most, if not all, living organisms is the ability to maintain levels of carbon dioxide (CO2). Of particular importance is the ability of many animals to sense and respond to high levels of CO2 by either attraction or aversion [1,2,3,4,5]. High levels of CO2 (hypercapnia) impair alveolar epithelial function of the lungs by activating the stress sensor AMPK, which leads to Na,K-ATPase endocytosis, impaired cell proliferation, and loss of distal lung epithelial function [6,7,8,9,10]. Cyclic AMP (cAMP) signaling plays a role in the response of mammalian cells to elevated CO2 levels [15,16,17]. The molecular pathways mediating the responses to hypercapnia are the focus of intensive research (see [11,18] and review in [19])
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